The eating disorders Anorexia Nervosa and Bulimia Nervosa are serious psychiatric illnesses that affect a significant number of women and that are associated with substantial morbidity and mortality. New approaches to understanding the mechanisms that contribute to the persistence of these disorders are sorely needed. Several lines of evidence suggest that abnormalities in ingestive behavior characteristic of these disorders bear similarities at a phenomenological and/or pathophysiological level to substance use disorders. Building on current understanding of mechanisms of addiction and on paradigms successfully employed to examine animal eating behavior, the proposed work will critically examine mechanisms that may underlie the development and persistence of human eating disorders. The proposed work is translational at two levels: first, from models of drug addiction to models of abnormal ingestive behavior, and, second, between models of ingestive behavior in laboratory animals and eating disorders in humans. This application grows out of a developmental grant which established collaboration among basic and clinical researchers with expertise in feeding neuroscience, addiction neuroscience, and eating disorders, with a focus on eating disorders. Based on paradigms developed under this collaboration, the current application proposes to examine factors that may contribute to the persistence of human eating disorders, focusing on the role of food reward, and on dopaminergic and opioid systems. The first specific aim of the proposed work is to identify and characterize behavioral indices of the motivating and rewarding effects of food in women with eating disorders and appropriate control subjects. The second aim is to investigate changes in dopamine release and receptor density, and in opioid receptor density via PET in the same populations. PUBLIC HEALTH RELEVANCE: The proposed research will provide new information on mechanisms underlying the persistence of eating disorders and the resemblance of these disorders to disorders of substance abuse. Knowledge of these mechanisms will provide a scientific foundation for the development of more effective treatment interventions.